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Therapeutic Platforms: Cancer, HIV, Other
Indications
Cancer
Every individual’s cancer is unique. Therefore, the most effective
treatment is one customized to a particular disease’s genetic configuration.
Argos’ core technology offers an ideal cancer therapy in that it
captures the complete genetic information of tumors, loads a patient’s
own dendritic cells with the total tumor RNA and uses these dendritic cells
to trigger a desired immune response.
The Challenge of Cancer: Individual
Cancers and Mutations
Genetic mutations and chromosomal abnormalities are commonly associated
with human cancers. Unfortunately, since the genetic mutations leading
to the development of cancer are often random events, every patient's
tumor can contain a unique repertoire of antigens. This characteristic
of human cancer requires that each patient's immune system be primed
to recognize the specific antigens present.
To address the challenge of
the unique genetic profile of each cancer and the genetic mutations of
that cancer, the Argos RNA-loaded DC immunotherapeutic is customized to
the unique antigenic repertoire of each patient's tumor, equipping the
immune system to recognize and fight that particular disease. These immunotherapeutics
preclude the need to identify or isolate specific tumor antigens and enable
targeting of unknown tumor antigens and treatment of patients from whom
only a minute amount of tumor material can be obtained.
Creating a Personalized
Cancer Product
Argos’ RNA-loaded DC immunotherapeutics start with precursors of
the patient's dendritic cells, which, when matured for the immunotherapeutic,
are currently considered the most effective antigen-presenting cells within
the immune system. Argos is then able to amplify tumor RNA from the patient
(whether from the primary tumor site, distant metastatic sites or from
tumor cells present in circulation) and transfect the patient's dendritic
cells with the patient's tumor RNA. This process offers the ability for
most cancer types at any stage of disease to be target opportunities for
the Company's cancer immunotherapeutic approach.
Unique Advantages
- Dendritic cells transfected with RNA-encoding tumor antigens have
been shown to stimulate potent immune cell responses equal or superior
to other competing approaches
- The immunotherapeutic is completely autologous (derived from the
patient’s body), potentially offering maximum safety with minimal
side effects
- The immunotherapeutic targets the entire antigenic repertoire of
the tumor including ‘private mutations’ unique to that
patient
- A single production run makes enough product to continuously treat
the patient for several years
- Production requires only a minute tumor specimen, allowing treatment
of earlier stage and later stage patients
- The manufacturing process is optimized for ‘day-old’ monocytes,
allowing for centralized manufacturing that provides the flexibility
to access patients and clinical sites nationwide
- Formulation requires no specialized manipulation at the clinical
sites, maximizing site participation (thaw in vial, load syringe, inject)
HIV & OTHER INFECTIOUS DISEASES
Chronic viral infections, such as those caused by human immunodeficiency
virus (HIV) and hepatitis C virus (HCV), are difficult to treat and often
incurable. Argos is applying its proprietary process to transfect dendritic
cells with patients’ viral RNA antigens, promoting immune responses
perfectly matched to the patient’s unique viral variants.
Argos’ proprietary
methodology utilizes small plasma samples from infected patients to amplify
large quantities of messenger RNA that encode selected viral antigens.
This technique has the added advantage of amplifying the multitude of patient-specific
viral variants evolving in the infected patient, allowing for the creation
of a therapy perfectly suited to the individual. Therefore, the viral sequences
presented to the immune system are completely compatible with the virus
that has infected the host. The simultaneous presence of autologous viral
sequences and dendritic cells should result in a novel immune response
that potentially has a greater probability of success in controlling residual
virus or a rebound of virus following the cessation of therapy.
Studies
published in Nature Medicine and The Journal of Infectious Diseases have
demonstrated how patient-specific immunotherapeutic approaches similar
to Argos’ have the potential to be effective treatment for people
with chronic HIV infection. Click here
In October 2006, Argos was awarded a $21M National Institutes of Health (NIH)
contract to develop its immunotherapy candidates. In addition to determining
the immunogenicity of its HIV product currently in the clinic, the goal of
the five-year contract is to subsequently develop then test in the clinic
even more potent next generation product candidates.
Argos believes its RNA-based technology can also
be used to create immunotherapies for other chronic infectious diseases
that don’t respond to current treatments. Infections such as hepatitis
C virus (HCV) and herpes represent some of the largest and most significant
areas of unmet medical need. In fact, any disease subject to immune surveillance
is potentially addressable.
Unique Advantages
- The immunotherapeutic can be comprised of any number of strategically
selected viral antigens (chosen to not adversely affect the biology
of dendritic cells)
- Amplification of viral antigens includes patient-specific dominant
and quasispecies (important for highly mutagenic viruses such as HIV
and HCV)
- Immune responses generated are 100% relevant for that patient
- Production requires only a small plasma sample that can be obtained
during leukapheresis
- If virus escape occurs at some point post-treatment, the product
can be ‘updated’ using a new plasma sample
- Argos knows of no other dendritic cell-based technology that could
feasibly produce an autologous anti-viral immunotherapeutic
OTHER INDICATIONS
In addition to its core RNA-loaded dendritic
cell technology, Argos has leveraged its dendritic cell expertise to develop
additional novel technologies with applications for transplantation rejection
and autoimmune disorders.
Programs in Transplantation and Autoimmune Disorders
The Company is developing a soluble protein — CD83 — shown
to be an effective immunosuppressant in several mouse model systems. Preliminary
data suggest that CD83 can be developed to treat multiple sclerosis, autoimmune
diabetes and transplantation rejection. As a result of an agreement with
Beckman Coulter, Argos gained exclusive therapeutic use rights for CD83,
including use as a therapy for autoimmune disorders and transplant rejection.
Strikingly,
CD83 distinguishes itself from other immunosuppressants, whether FDA approved
or in development, in that it does not appear to require chronic administration
and does not leave the patient globally immunosuppressed.
In February 2005,
Argos received a $1 million grant from the Alliance for Lupus Research
to develop a monoclonal antibody-based therapy for the treatment of systemic
lupus erythematosis (SLE). Argos has identified and validated a molecular
target — Interferon-alpha — as a trigger
for the onset and maintenance of SLE, and as having a role in the onset
of psoriasis. In early 2006, the Company partnered this program with Novo
Nordisk, which will continue pre-clinical development efforts to humanize
the antibody and manufacture clinical-grade material in preparation for
clinical trials.
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